Inhibition of noradrenergic signaling in rodent orbitofrontal cortex impairs the updating of goal-directed actions

  1. Juan Carlos Cerpa
  2. Alessandro Piccin
  3. Margot Dehove
  4. Marina Lavigne
  5. Eric J Kremer
  6. Mathieu Wolff
  7. Shauna L Parkes  Is a corresponding author
  8. Etienne Coutureau  Is a corresponding author
  1. CNRS, University of Bordeaux, France
  2. CNRS, University of Montpellier, France

Abstract

In a constantly changing environment, organisms must track the current relationship between actions and their specific consequences and use this information to guide decision-making. Such goal-directed behavior relies on circuits involving cortical and subcortical structures. Notably, a functional heterogeneity exists within the medial prefrontal, insular, and orbitofrontal cortices (OFC) in rodents. The role of the latter in goal-directed behavior has been debated, but recent data indicate that the ventral and lateral subregions of the OFC are needed to integrate changes in the relationships between actions and their outcomes. Neuromodulatory agents are also crucial components of prefrontal functions and behavioral flexibility might depend upon the noradrenergic modulation of the prefrontal cortex. Therefore, we assessed whether noradrenergic innervation of the OFC plays a role in updating action-outcome relationships in male rats. We used an identity-based reversal task and found that depletion or chemogenetic silencing of noradrenergic inputs within the OFC rendered rats unable to associate new outcomes with previously acquired actions. Silencing of noradrenergic inputs in the prelimbic cortex or depletion of dopaminergic inputs in the OFC did not reproduce this deficit. Together, our results suggest that noradrenergic projections to the OFC are required to update goal-directed actions.

Data availability

All data generated or analysed during this study are included in the supporting file

Article and author information

Author details

  1. Juan Carlos Cerpa

    CNRS, University of Bordeaux, Bordeaux, France
    Competing interests
    No competing interests declared.
  2. Alessandro Piccin

    CNRS, University of Bordeaux, Bordeaux, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9566-3808
  3. Margot Dehove

    CNRS, University of Bordeaux, Bordeaux, France
    Competing interests
    No competing interests declared.
  4. Marina Lavigne

    Institut de Génétique Moléculaire de Montpellier, CNRS, University of Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  5. Eric J Kremer

    Institut de Génétique Moléculaire de Montpellier, CNRS, University of Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  6. Mathieu Wolff

    CNRS, University of Bordeaux, Bordeaux, France
    Competing interests
    Mathieu Wolff, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3037-3038
  7. Shauna L Parkes

    CNRS, University of Bordeaux, Bordeaux, France
    For correspondence
    shauna.parkes@u-bordeaux.fr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7725-8083
  8. Etienne Coutureau

    CNRS, University of Bordeaux, Bordeaux, France
    For correspondence
    etienne.coutureau@u-bordeaux.fr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6695-020X

Funding

Agence Nationale de la Recherche (CE37-0019 NORAD)

  • Eric J Kremer
  • Etienne Coutureau

Fondation pour la Recherche Médicale (ECO20160736024)

  • Juan Carlos Cerpa

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experiments were performed in accordance with current French (Council directive 2013-118, February 1, 2013) and European (directive 2010-63, September 22, 2010, European Community) laws and policies regarding animal experimentation. The experiments received approval from the local Bordeaux Ethics Committee (CE50).

Reviewing Editor

  1. Laura A Bradfield, University of Technology Sydney, Australia

Publication history

  1. Preprint posted: July 1, 2022 (view preprint)
  2. Received: July 5, 2022
  3. Accepted: February 17, 2023
  4. Accepted Manuscript published: February 20, 2023 (version 1)
  5. Version of Record published: March 6, 2023 (version 2)

Copyright

© 2023, Cerpa et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Juan Carlos Cerpa
  2. Alessandro Piccin
  3. Margot Dehove
  4. Marina Lavigne
  5. Eric J Kremer
  6. Mathieu Wolff
  7. Shauna L Parkes
  8. Etienne Coutureau
(2023)
Inhibition of noradrenergic signaling in rodent orbitofrontal cortex impairs the updating of goal-directed actions
eLife 12:e81623.
https://doi.org/10.7554/eLife.81623

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